This research proposal is aimed at investigating mechanisms that predispose to chronic pulmonary disease. Studies of alpha-l-antitrypsin deficiency will be continued in order to perfect simplified methods for its detection that would allow generalized availability to clinical laboratories. Mechanisms involved in the development of antitrypsin deficiency will be studied, and the usefulness of screening for antitrypsin deficiency in junior high school age subjects will be investigated. Other mechanisms being studied include possible genetic variations in leukocyte protease content as a predisposing factor for pulmonary emphysema, and aryl-hydrocarbon-hydroxlase induction as a possible predisposing factor for lung cancer. The role of lymphocyte transformation during culture will be looked at as a potential factor in cystic fibrosis, both in diagnosis and as an underlying abnormality in the disease. Finally, our recent discovery of elevated angiotensin-converting-enzyme (ACE) in patients with sarcoidosis will be further investigated to determine the usefulness of this test in diagnosis and the role of the enzyme elevation in the pathogenesis of the disease.